There is no effective method or drug for treating nephritis and artificial dialysis is carried out in patients with chronic nephritis and reduced renal function. Chronic glomerulonephritis is said to play a main role in introducing the artificial dialysis and amounts to about 40% of the original diseases of patients introducing the artificial dialysis. Under these circumstances, the development of excellent agents for treating nephritis is expected from the standpoint of medical administration.
TGF-.beta. (transforming growth factor-.beta.) acts on various cells such as fibroblasts to enhance the production of extracellular matrices such as collagen, and prevents the degradation of the extracellular matrices by proteases. Further, it has been reported to promote the deposition of the extracellular matrices onto cell surfaces. Thus, diseases associated with TGF-.beta. may include liver cirrhosis, pulmonary or other fibrosis, nephritis, chronic renal insufficiency, diabetic nephropathy, and retinopathy.
Therefore, it is expected that any substances inhibiting TGF-.beta. would be effective for such fibrous diseases.
Japanese Patent Laid Open Publication No. 8-333249 discloses that compounds represented by the following formula (A): ##STR2##
wherein A is a single bond or --NH--, E is --OCO-- or --COO--, Phe is a 1,4-phenylene group, Ar--R.sup.1 is a phenyl group substituted a group represented by the following formula: ##STR3##
in which Z is a single bond, or a methylene, ethylene or vinylene group, R.sup.2 is a hydrogen atom or a C.sub.1-4 alkyl or --CH.sub.2 CONR.sup.3 R.sup.4 group, R.sup.3 and R.sup.4 independently being a hydrogen atom or a C.sup.1-4 alkyl group, R.sup.5 and R.sup.6 independently are a hydrogen atom or a C.sub.1-4 alkyl group, R.sup.7 is a C.sub.2-6 alkenyl group, and R.sup.8 is --(CH.sub.2).sub.n --COOR.sup.9, n being 0 or an integer of 1 to 4 and R.sup.9 being a hydrogen atom or a C.sub.1-4 alkyl group, or salts thereof are useful agents for inhibiting release, activation and synthesis of TGF-.beta.. However, there is no description on the pyridylacrylamide derivatives represented by the formula (I) below which are used as effective ingredients in the pharmaceutical compositions of the present invention.
With respect to the pyridylacrylamide derivatives, on the other hand, WO93/04035 (Japanese Patent Laid Open Publication No. 6-510030) describes the compound represented by the following formula (B): EQU Ar.sup.3 --CH.dbd.CH--CO--NHCH.sub.2 --Ar.sup.4 (B)
wherein Ar.sup.3 is a 3-pyridyl group and Ar.sup.4 is a 3,5-di-tert-butyl-4-hydroxyphenyl group as an example of many 3,5-di-tert-butyl-4-hydroxyphenyl derivatives, and shows that the compound is useful as agents for treating metabolic diseases, such as anti-atherosclerosis agents, and may act anti-inflammatory and cytophylatically as well as antasthmatically. However, there is no description suggesting that the compound (B) is useful as anti nephritic agents or TGF-.beta. inhibitors.